17-28364299-A-G

Variant names:

• chr17-28364299-A-G
• rs9910163
• NM_001080837.4:c.542T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080837.4(SEBOX):​c.542T>C​(p.Leu181Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,604,922 control chromosomes in the GnomAD database, including 495,899 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (52846 hom., cov: 32)
  • Exomes 𝑓: 0.78 (443053 hom.)
• Consequence: SEBOX NM_001080837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 26 publications found

Genes affected

SEBOX (HGNC:32942): (SEBOX homeobox) Homeodomain proteins, such as SEBOX, play a key role in coordinating gene expression during development (Cinquanta et al., 2000 [PubMed 10922053]).[supplied by OMIM, Mar 2008]

ENSG00000273171 (HGNC:):

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.989246E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080837.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEBOX	NM_001080837.4	MANE Select	c.542T>C	p.Leu181Ser	missense	Exon 3 of 3	NP_001074306.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEBOX	ENST00000536498.6	TSL:5 MANE Select	c.542T>C	p.Leu181Ser	missense	Exon 3 of 3	ENSP00000444503.3
	ENSG00000273171	ENST00000555059.2	TSL:4	c.*393T>C		3_prime_UTR	Exon 4 of 4	ENSP00000452347.3
	ENSG00000258924	ENST00000591482.1	TSL:2	n.555+3452A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125768 AN: 152076 Hom.: 52793 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.846

GnomAD2 exomes AF: 0.795 AC: 187261 AN: 235462 AF XY: 0.794

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.773

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.996

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.762

Gnomad OTH exome AF: 0.788

GnomAD4 exome AF: 0.779 AC: 1131350 AN: 1452728 Hom.: 443053 Cov.: 47 AF XY: 0.779 AC XY: 562497 AN XY: 721670

African (AFR) AF: 0.967 AC: 32283 AN: 33368

American (AMR) AF: 0.773 AC: 33442 AN: 43242

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 20509 AN: 25976

East Asian (EAS) AF: 0.996 AC: 39212 AN: 39356

South Asian (SAS) AF: 0.830 AC: 70176 AN: 84576

European-Finnish (FIN) AF: 0.684 AC: 36157 AN: 52832

Middle Eastern (MID) AF: 0.821 AC: 4723 AN: 5752

European-Non Finnish (NFE) AF: 0.765 AC: 846757 AN: 1107540

Other (OTH) AF: 0.800 AC: 48091 AN: 60086

GnomAD4 genome AF: 0.827 AC: 125881 AN: 152194 Hom.: 52846 Cov.: 32 AF XY: 0.823 AC XY: 61230 AN XY: 74404

African (AFR) AF: 0.960 AC: 39879 AN: 41540

American (AMR) AF: 0.812 AC: 12423 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2741 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5135 AN: 5168

South Asian (SAS) AF: 0.834 AC: 4020 AN: 4822

European-Finnish (FIN) AF: 0.669 AC: 7089 AN: 10594

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51810 AN: 67990

Other (OTH) AF: 0.848 AC: 1785 AN: 2106

Alfa AF: 0.790 Hom.: 144430

Bravo AF: 0.844

TwinsUK AF: 0.764 AC: 2832

ALSPAC AF: 0.765 AC: 2949

ESP6500AA AF: 0.959 AC: 4023

ESP6500EA AF: 0.777 AC: 6566

ExAC AF: 0.795 AC: 96122

Asia WGS AF: 0.905 AC: 3145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.88
DANN	Benign	0.72
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	9.0e-7	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.094
PrimateAI	Benign	0.34	T
REVEL	Benign	0.23
Sift4G	Benign	0.77	T
Vest4		0.071
ClinPred		0.0016	T
GERP RS		2.1
gMVP		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9910163; hg19: chr17-26691321; COSMIC: COSV52647723; COSMIC: COSV52647723;